Marc Gunter

Ph.D

International Agency for Research on Cancer

Section Head

PLCO (Learn more about this study)

PLCO-397

Oct 11, 2018

Diabetes and Cancer Initiative

Type 2 diabetes mellitus (T2D) and cancer are two of the most significant causes of mortality and morbidity worldwide. It has been estimated that approximately 387 million individuals or 9% of those aged 25 years or over are diabetic while around 14 million new cases of cancer are diagnosed across worldwide each year. With a growing aging population across most regions of the world, it is expected that these figures will rise substantially in the coming decades. Interestingly, there is now an emerging consensus from experimental and observational studies that cancer and T2D are linked and may share common etiologic pathways. Cancer and T2D are more commonly co-diagnosed in the same individual than would be expected by chance, even after adjustment for age, and there is epidemiological evidence indicating that diabetics have increased risk of developing a number of common malignancies including liver, pancreatic, endometrial, colorectal, postmenopausal breast, and bladder cancers. Evidence is less conclusive for other cancers such as those of the esophagus, kidney, and thyroid gland and for leukemia; however, few individual studies have been of sufficient size to investigate these tumor types with precision. Further, a critical, and as of yet, unanswered question, is whether the T2D-cancer association is primarily due to shared risk factors (obesity, diet, aging, sedentary lifestyle), or whether T2D itself, and the specific metabolic derangements that characterize T2D (e.g. hyperinsulinemia and hyperglycemia) increase risk of certain cancer types. There is also limited data on the impact of T2D on survival among cancer patients, and whether diabetes treatments can modulate cancer development and clinical course. To significantly advance knowledge on the potential role of diabetes in cancer incidence and survival, data from 28 prospective cohort studies that participate in the NCI Cohort Consortium will be pooled and used to address the following specific aims: (i) To quantify the association of T2D with cancer incidence at all anatomic sites with appropriate control for shared risk factors (e.g. body habitus); (ii) To investigate the association of T2D with cancer survival while accounting for clinical variables (e.g. tumor stage and grade); (iii) To explore the impact of diabetes treatments on cancer development and survival. The proposed study, which will collectively include data from more than 3 million individuals, is unprecedented in terms of sample size and availability of prospectively collected demographic, clinical and lifestyle data and represents a significant opportunity to gain substantial knowledge on the relationship between these two major comorbidities.

1. To quantify the association of T2D with cancer development - We will exploit existing data from 28 prospective cohort studies comprising more than 3 million individuals and including >230,000 diabetics and >314,000 incident cancer cases to provide more definitive evidence on the relationship of T2D with cancer risk. The large sample size will enable us to quantify the associations of T2D with all major cancers with a high degree of precision while accounting for important confounding factors and to investigate associations between T2D and less common malignancies, and to determine whether the T2D-cancer relationship differs according to non-modifiable risk factors (age, gender, ethnicity) and modifiable risk factors (body habitus, diet, physical activity, smoking, alcohol).

2. To investigate the association of diabetes diagnosis with cancer survival - In this analysis we will significantly further knowledge on this important question which could have a significant impact on surveillance and treatment modalities in cancer patients. Among the approximately 314,000 cancer patients with available data across the consortium, an estimated 110,000 have died. We propose to investigate the association of T2D with all-cause and cancer-related death among these patients, while accounting for patho-clinical characteristics such as tumor stage and grade.

3. To explore the impact of diabetes treatments on cancer development and survival - There is emerging evidence that some forms of diabetes treatment may be associated with reduced risk of certain malignancies. We propose to investigate the association of diabetes treatments in relation to cancer risk and survival by utilizing pooled data across the cohorts to determine: 1) whether diabetes treatments are associated with cancer incidence; 2) whether diabetes treatments are associated with cancer survival and other outcomes after cancer diagnosis; 3) whether these relationships are modified by other major cancer risk factors, in particular obesity; 4) explore whether these associations vary by cancer stage, grade, anatomical location or histological characteristics.